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General OB/GYN Open Access

Demographic and lifestyle determinants of time spent in physical activity among Malaysian adolescents

Cheah YK et al., 2019Int J Pediatr Adolesc Med

The objective of the present study is to examine factors affecting time spent in physical activity among adolescents in Malaysia. A nationally representative data of adolescents that consists of 25399 respondents is used. The demographic (age, gender, education) and lifestyle (fruits and vegetables consumption, carbonated soft drink consumption, cigarette smoking, alcohol drinking, sex behaviour, participation in physical education class, obesity) determinants of physical activity are assessed using binomial regression. The results show that age is negatively associated with time spent in physical activity. However, being male and education levels are positively related to time spent in physical activity. Having unhealthy lifestyle and being obese are associated with low levels of physical activity. Physical education seems to promote participation in physical activity. In conclusion, demographic and lifestyle factors play an important role in determining levels of physical activity among adolescents. In order to reduce the prevalence of physically inactive adolescents, policy makers should focus primarily on late adolescents, females, adolescents who engage in unhealthy lifestyle and seldom attend physical education classes, as well as obese adolescents.

Reproductive EndocrinologyGeneral OB/GYN Open Access

Hemoperitoneum after Ovulation in Systemic Lupus Erythematosus and Autoimmune Thrombocytopenia

Buskmiller C et al., 2019Case Rep Obstet Gynecol

Three prior cases of hemoperitoneum associated with immune thrombocytopenia (ITP) have been reported in adolescents. This reports a case of hemoperitoneum after ovulation in an adult. A 34-year-old nulligravida presented with abdominal pain after a heavy period and rebound tenderness. Urine beta-hCG was negative, hemoglobin was 5.4, and platelet count was zero. CT revealed hemoperitoneum and contrast blush surrounding the left ovary. She was treated for newly diagnosed systemic lupus erythematosus and steroid-refractory ITP. Her platelet count and symptoms improved. Hemoperitoneum after ovulation in ITP is rare; this represents the first adult case in the literature and reviews differential diagnosis of thrombocytopenia. The obstetrician/gynecologist is part of a multidisciplinary team caring for patients with bleeding of gynecological origin and should withhold surgical intervention for hemoperitoneum when medical therapy is warranted.

Reproductive EndocrinologyGeneral OB/GYN

Naltrexone: A History and Future Directions

Srivastava AB et al., 2019Cerebrum

Trying to kick drug addiction without medicines is said to be like relying on willpower to overcome diabetes or asthma. Enter naltrexone, which has been around since 1984 and reduces the cravings for drugs and alcohol by fine-tuning the brain's chemical reward system. Why has it recently increased in popularity? How does it compare to similar strategies? Has it made a difference? Our authors, who have long studied addiction and the brain, confront a drug and alcohol addiction problem that today kills more Americans each day than gun violence or car accidents.

Research Open Access

Textile Contact Dermatitis: How Fabrics Can Induce Dermatitis

Svedman C et al., 2019Current Treatment Options in Allergy

Textile dermatitis can sometimes be difficult to diagnose due to the fact that it is difficult to clinically suspect, and when allergic, patch test correctly and advice the patient as to what garments to avoid. The textile fibres as such are rarely the causative agent. Allergic contact dermatitis due to textiles is primarily caused by substances that are used to give the material certain qualities or performances. The textile dye mix, now in the baseline series, has proven to be a useful tool in diagnosing allergic contact dermatitis but additional patch testing with own material is advocated. Future research will hopefully facilitate the diagnostic procedure. This review is a short update on textile dermatitis, both irritant and allergic, the present recommendations regarding patch testing when suspecting contact allergy and the advice to give to those allergic that will hopefully help the clinician in daily work.

Bone HealthQuality of Life ImpactProspective Cohort StudiesFracture Outcomes

Incident Fragility Fractures Have a Long-Term Negative Impact on Health-Related Quality of Life of Older People: The Canadian Multicentre Osteoporosis Study

Sayem Borhan et al., 2019J Bone Miner Res

Although the short-term impact of incident fragility fractures on health-related quality of life (HRQL) of older people has been confirmed, we lack long-term evidence. We explored the impact of incident fragility fractures on HRQL, among people aged 50 years and older, using 10-year prospective data from the Canadian Multicentre Osteoporosis Study (CaMos). This study was based on data from 7753 (2187 men and 5566 women) participants of CaMos. The HRQL, measured through the Health Utility Index (HUI), was captured at baseline and year 10. The incident fragility fractures were recorded over 10 years of follow-up at spine, hip, rib, shoulder, pelvis, or forearm. Multivariable regression analysis was conducted to measure the mean difference, termed as deficit, in the HUI scores for participants with and without fractures. We examined the effects of single or multiple fragility fractures, time (fractures that occurred between year 1 to 5 and 6 to 10) and recovery to the prefracture level. Incident spine and hip fractures were associated with significant deficits (varied from -0.19 to -0.07) on the HUI scores. Hip and spine fractures were associated with negative impact on mobility, self-care, and ambulation. Fractures that occurred closer to the follow-up assessment were associated with significant impact on HRQL compared to fractures occurring a long time before it, except for hip fracture (deficits lasted 5 years or longer). Similarly, multiple hip (-0.14), spine (-0.16), and rib (-0.21) fractures significantly impacted the HRQL of women. Women with a hip fracture never recovered to their prefracture level score (OR = 0.41; 95% confidence interval [CI], 0.19 to 0.98). Our analysis suggests that single and multiple hip fractures as well as multiple spine and rib fractures strongly impact the HRQL of older people over a prolonged period of time.

Research

Comparison of body weight among hormonal and non-hormonal users in a Malaysian cohort

Ibrahim H et al., 2019Journal of Taibah University Medical Sciences

Weight gain remains an issue for contraceptive users due to the high prevalence of obesity. This retrospective study compares the weight gain between hormonal and non-hormonal contraceptive users in government health clinics in Kota Bharu, Kelantan, Malaysia. A total of 380 women who had used the same contraceptive method for at least twelve months were recruited in this study. Covariance analysis was done to compare the weight gain between hormonal and non-hormonal contraceptive users, while studying the same confounders [age, household income, number of pregnancies, and baseline body mass index (BMI)]. Hormonal methods were more commonly used. The mean weight gain among hormonal users (adjusted mean 2.85, 95% CI 2.45, 3.24) was significantly higher than non-hormonal users (adjusted mean 0.46, 95% CI -0.73, 1.65; p-value <0.001), after controlling for age, household income, number of pregnancies, and baseline BMI. The possibility of weight gain following the use of hormonal methods should be investigated and non-hormonal methods should be considered to prevent weight gain. أهداف البحث: لا تزال زيادة الوزن قضية، لمستخدمات وسائل منع الحمل بسبب زيادة الوزن وانتشار معدل السمنة. تهدف هذه الدراسة المرجعية لمقارنة زيادة الوزن بين موانع الحمل الهرمونية وغير الهرمونية في عيادات الصحة الحكومية في مدينة بهارو، كلنتان، ماليزيا. طرق البحث: تم مشاركة ما مجموعه ٣٨٠ سيدة من اللواتي استخدمن نفس وسيلة منع الحمل لمدة ١٢ شهرا في هذه الدراسة. تم عمل تحليل التباين لمقارنة زيادة الوزن بين مستخدمات موانع الحمل الهرمونية وغير الهرمونية، أثناء دراسة نفس العوامل (العمر، ودخل الأسرة، وعدد مرات الحمل ومؤشر كتلة الجسم الأساسي). النتائج: كانت الطرق الهرمونية هي الأكثر شيوعا. متوسط زيادة الوزن بين مستخدمات الهرمون (المتوسط المعدل ٢.٨، فاصل الثقة ٩٥٪ ٢.٤٥، ٣.٢٤) أعلى بكثير من مستخدمات الطرق غير الهرمونية (المتوسط المعدل ٠.٤٦، فاصل الثقة ٠.٧٣-، ١.٦٥) بعد التحكم في العمر، ودخل الأسرة، وعدد مرات الحمل ومؤشر كتلة الجسم الأساسي. الاستنتاجات: ينبغي التحقق من إمكانية زيادة الوزن بعد استخدام الطرق الهرمونية وينبغي النظر في خيارات أخرى من الطرق غير الهرمونية للحد من زيادة الوزن.

NaProTECHNOLOGYSeminary and Clergy FormationNFP Curriculum OutcomesHumanae Vitae Implementation

A Quantitative Self-Assessment of Seminarians' Response to a Curriculum Addition on Marriage, Sexuality, FertilityCare, and Naprotechnology: The Kenrick-Glennon Experience (2006-2015)

Daly KD et al., 2019Linacre Q

A special course on Marriage, the Family and Human Sexuality was established at Kenrick-Glennon Seminary in St. Louis so as to assist the seminarians in their better understanding of the Church's teaching relative to natural methods of family planning and women's health care. This article compares the response at the beginning of this three-credit semester course to the same seven-item questionnaire given at the conclusion of the course. The preand postcourse scores were calculated for each of the questions. The scores obtained after the course were all significantly higher than they were before the course with p values ranging from 0.01 to <0.0001. Four of the items showed marked improvement including an understanding of the church's teaching related to natural methods, current methods of natural family planning, the impact of a natural method on a couple's marriage, and also the impact of a natural method on family life. Statistically significant improvement was also seen in their understanding of the topic of natural family planning and the Creighton Model System and its relevance toward the seminarian's vocation, the use of the methods to either achieve or avoid pregnancy, and how contraception and abortion are linked. In these last three items, the level of statistical significance was quite high, although not as high as the other four items. There were 104 seminarians over an eight-year period of time, who provided answers to these questions, both before and after the course. This course was modeled after a course that was initiated at the Pope Paul VI Institute for the Study of Human Reproduction, which was for priests, seminarians, and Catholic leaders, titled Love & Life Unlimited. This is an evaluation of a ten-point, seven-question questionnaire that was utilized at the beginning of a course at Kenrick Seminary in Marriage, Sexuality, Creighton Model and NaProTECHNOLOGY. The same questionnaire was given to the students at the beginning of the course and then two to three months later at the conclusion of the three-credit course. The results show that there is a significant improvement in the seminarians' knowledge and general attitude about natural methods of family planning and suggests that such courses would be beneficial to establish in seminaries throughout the country.

Bone HealthRisk Factors in DiabetesFrailty and Fracture RiskFracture Prediction

Frailty and Risk of Fractures in Patients With Type 2 Diabetes

Guowei Li et al., 2019Diabetes Care

We aimed to explore whether frailty was associated with fracture risk and whether frailty could modify the propensity of type 2 diabetes toward increased risk of fractures.Research design and methodsData were from a prospective cohort study. Our primary outcome was time to the first incident clinical fragility fracture; secondary outcomes included time to hip fracture and to clinical spine fracture. Frailty status was measured by a Frailty Index (FI) of deficit accumulation. The Cox model incorporating an interaction term (frailty × diabetes) was used for analyses. The analysis included 3,149 (70% women) participants; 138 (60% women) had diabetes. Higher bone mineral density and FI were observed in participants with diabetes compared with control subjects. A significant relationship between the FI and the risk of incident fragility fractures was found, with a hazard ratio (HR) of 1.02 (95% CI 1.01-1.03) and 1.19 (95% CI 1.10-1.33) for per-0.01 and per-0.10 FI increase, respectively. The interaction was also statistically significant (P = 0.018). The HR for per-0.1 increase in the FI was 1.33 for participants with diabetes and 1.19 for those without diabetes if combining the estimate for the FI itself with the estimate from the interaction term. No evidence of interaction between frailty and diabetes was found for risk of hip and clinical spine fractures. Participants with type 2 diabetes were significantly frailer than individuals without diabetes. Frailty increases the risk of fragility fracture and enhances the effect of diabetes on fragility fractures. Particular attention should be paid to diabetes as a risk factor for fragility fractures in those who are frail.

Contraception/ComparisonMedical Eligibility CriteriaCoexisting Medical ConditionsACOG Practice Bulletins

ACOG Practice Bulletin No. 206: Use of Hormonal Contraception in Women With Coexisting Medical Conditions

ACOG, 2019Obstet Gynecol

Although numerous studies have addressed the safety and effectiveness of hormonal contraceptive use in healthy women, data regarding women with underlying medical conditions or other special circumstances are limited. The U.S. Medical Eligibility Criteria (USMEC) for Contraceptive Use, 2016 (), which has been endorsed by the American College of Obstetricians and Gynecologists, is a published guideline based on the best available evidence and expert opinion to help health care providers better care for women with chronic medical problems who need contraception. The goal of this Practice Bulletin is to explain how to use the USMEC rating system in clinical practice and to specifically discuss the rationale behind the ratings for various medical conditions. Contraception for women with human immunodeficiency virus (HIV) (); the use of emergency contraception in women with medical coexisting medical conditions, including obesity, (); and the effect of depot medroxyprogesterone acetate (DMPA) on bone health () are addressed in other documents from the American College of Obstetricians and Gynecologists.

Contraception/ComparisonDepression and Mood DisordersNational Comorbidity Survey AnalysisOral Contraceptive Safety

Oral contraceptive use and depression among adolescents

McKetta S et al., 2019Ann Epidemiol

Depression is a prevalent health problem affecting U.S. women. Oral contraceptive pills (OCPs) are commonly used for pregnancy prevention, and evidence is mixed regarding any increased risk for incident depression among users, particularly adolescents. We examined the relationship between OCP use and depressive disorders among female adolescents using validated, structured interview assessments in a general population sample of adolescents in the National Comorbidity Survey-Adolescent Supplement. Respondents were 4765 female adolescents with no history of pregnancy who reported current OCP use, lifetime OCP use, and age of OCP initiation. Lifetime and current depressive disorders, including major depressive disorder and depressive episodes, were assessed by lay interviewers. In logistic regression models adjusted for a range of confounders, there was no relationship between ever using OCPs and lifetime depressive disorder (OR 1.10, 95% CI 0.88-1.37), nor current use of OCPs and current depressive disorder (OR 0.82, 95% CI 0.50-1.35). Using survival analysis for age-of-onset data, we found that OCP use is not associated with an increased risk of depressive disorders. In sum, use of OCPs in a general population sample of adolescents did not increase the risk of depressive disorders.

SurgeryCesarean Scar Defect RepairIsthmocele Diagnosis and ManagementLong-Term Scar Complications Open Access

Isthmocele: From Risk Factors to Management

Iannone P et al., 2019Rev Bras Ginecol Obstet

The aim of the present study was to perform a comprehensive review of the literature to provide a complete and clear picture of isthmocele-a hypoechoic area within the myometrium at the site of the uterine scar of a previous cesarean section-by exploring in depth every aspect of this condition. A comprehensive review of the literature was performed to identify the most relevant studies about this topic. Every aspect of isthmocele pathophysiology, clinical symptoms, classification, and diagnosis. Its treatment, both medical and surgical, has also been reported according to the actual literature data. Cesarean section is the most common surgical procedure performed worldwide, and one of the consequences of this technique is isthmocele. A single and systematic classification of isthmocele is needed to improve its diagnosis and management. Further studies should be performed to better understand its pathogenesis.

Research

Effect of progesterone administration on the prognosis of patients with severe traumatic brain injury: a meta-analysis of randomized clinical trials

Pan ZY et al., 2019Drug Design, Development and Therapy

The aim of this study was to assess the neuroprotective effect of progesterone administration on severe traumatic brain injury (TBI) for different follow-up periods and administration route by completing a meta-analysis of randomized clinical trials (RCTs). A systematic literature search of PubMed, Embase, and Cochrane databases and the Web of Science (from establishment of each to September 1, 2018) was performed to identify original RCTs that evaluated the associations between progesterone treatment and the prognosis of patients with severe TBI. Eight RCTs enrolling 2,251 patients with severe TBI were included. Within 3 months post-injury, patients with progesterone administration had a lower mortality (risk ratio [RR] =0.59; 95% CI [0.42-0.81], P=0.001) and better neurologic outcomes (RR =1.51; 95% CI [1.12-2.02], P=0.007) than those who received placebo. However, these differences did not persist at 6 months post-injury for mortality (RR =0.96; 95% CI [0.65-1.41], P=0.83) or neurologic outcomes (RR =1.09; 95% CI [0.93-1.27], P=0.31). The analysis stratified by administration route showed that beneficial effects were only observed in patients who received progesterone intramuscularly (RR =1.61, 95% CI [1.19-2.18], P=0.002); no benefit was observed with intravenous administration (RR =0.99, 95% CI [0.91-1.07], P=0.75). Progesterone administration improved the clinical outcomes of severe TBI patients within 3 months but may not have significant long-term benefits 6 months post-injury.

Bone HealthAdolescent Peak BMD AccrualBone Health EffectsProspective Controlled Studies Open Access

Adolescent use of combined hormonal contraception and peak bone mineral density accrual: A meta-analysis of international prospective controlled studies

Goshtasebi A et al., 2019Clin Endocrinol (Oxf)

Many women use combined hormonal contraceptives (CHC) during adolescence during which they are accruing peak areal bone mineral density (BMD) that relates to lifetime fracture risk. To build BMD requires formation with which CHC-related exogenous oestrogen may interfere. We compared peak BMD accrual in adolescents using and not using CHC. We performed literature searches for prospective published peer-reviewed articles providing 12to 24-month BMD change in adolescent (12to 19-year-old) women using CHC vs CHC-unexposed control women. Meta-analyses used random-effects models to assess BMD change rate at lumbar spine (LS) and other sites in adolescent CHC users vs CHC nonusers. Literature searches yielded 84 publications of which nine were eligible. Adolescent-only data were sought from cohorts with wider age inclusions. The 12-month LS meta-analysis with eight paired comparisons in 1535 adolescents showed a weighted mean BMD difference of -0.02 (95% confidence interval [CI]: -0.05 to 0.00) g/cm(2) in CHC-exposed adolescents (P = 0.04). The 24-month LS meta-analysis with five paired comparisons in 885 adolescents showed a highly significant weighted mean BMD difference of -0.02 (95% CI: -0.03 to -0.01) g/cm(2) in CHC-exposed adolescents (P = 0.0006). Heterogeneities by I(2) were 96% and 85%, respectively. Insufficient data for other bone sites precluded quantitative analysis. Given that adolescent exposure to CHC appears to be increasing, this evidence for potential impairment of peak spinal BMD accrual is of concern and suggests a potential public health problem. Randomized controlled trial data are needed to determine CHC effects on adolescent bone health.

Reproductive EndocrinologyTransgender Women TherapyCross-Sex HormonesProgesterone and Bone Formation

Progesterone Is Important for Transgender Women's Therapy-Applying Evidence for the Benefits of Progesterone in Ciswomen

Prior JC, 2019J Clin Endocrinol Metab

Although the 2017 Endocrine Society Guidelines for gender dysphoria stipulated that cross-sex hormone therapy (CHT) achieve gonadal steroid levels equivalent to those of a cisperson of the chosen sex, for transgender women (male-to-female gender dysphoria), current gonadal therapy is usually estradiol. Accumulated evidence indicates that normally ovulatory menstrual cycles are necessary for ciswomen's current fertility, as well as for later-life bone and cardiovascular health and the prevention of breast and endometrial cancers. Extensive past clinical experience with transgender women's CHT using estradiol/estrogen combined with progesterone/medroxyprogesterone and pioneering the addition of spironolactone. Comprehensive progesterone physiology research plus a brief review of transgender women's literature to assess current therapy and clinical outcomes, including morbidity and mortality. To emphasize that both ovarian hormones, progesterone as well as estradiol, are theoretically and clinically important for optimal transgender women's CHT. It is important to add progesterone to estradiol and an antiandrogen in transgender women's CHT. Progesterone (i) more rapid feminization, (ii) decreased endogenous testosterone production, (iii) optimal breast maturation to Tanner stages 4/5, (iv) increased bone formation, (v) improved sleep and vasomotor symptom control, and (vi) cardiovascular health benefits. Evidence has accrued that normal progesterone (and ovulation), as well as physiological estradiol levels, is necessary during ciswomen's premenopausal menstrual cycles for current fertility and long-term health; transgender women deserve progesterone therapy and similar potential physiological benefits.

Research

Hypothalamic-Pituitary-Ovarian Axis Disorders Impacting Female Fertility

Mikhael S et al., 2019Biomedicines

The hypothalamic-pituitary-ovarian (HPO) axis is a tightly regulated system controlling female reproduction. HPO axis dysfunction leading to ovulation disorders can be classified into three categories defined by the World Health Organization (WHO). Group I ovulation disorders involve hypothalamic failure characterized as hypogonadotropic hypogonadism. Group II disorders display a eugonadal state commonly associated with a wide range of endocrinopathies. Finally, group III constitutes hypergonadotropic hypogonadism secondary to depleted ovarian function. Optimal evaluation and management of these disorders is based on a careful analysis tailored to each patient. This article reviews ovulation disorders based on pathophysiologic mechanisms, evaluation principles, and currently available management options.

Bone HealthBisphosphonatesTreatment OutcomesProspective Cohort

Mortality risk reduction differs according to bisphosphonate class: a 15-year observational study

D Bliuc et al., 2019Osteoporos Int

In this prospective cohort of 6120 participants aged 50+, nitrogen-bisphosphonates but not non-nitrogen bisphosphonates were associated with a significant 34% mortality risk reduction compared to non-treated propensity score matched controls. These findings open new avenues for research into mechanistic pathways. Emerging evidence suggests that bisphosphonates (BP), first-line treatment of osteoporosis, are associated with reduced risks for all-cause mortality. This study aimed to determine the association between different BP types and mortality risk in participants with or without a fracture. A prospective cohort study of users of different BPs matched to non-users by propensity score (age, gender, co-morbidities, fragility fracture status) and time to starting the BP medication from the population-based Canadian Multicentre Osteoporosis Study from nine Canadian centres followed from 1995 to 2013. Mortality risk for bisphosphonate users vs matched non-users was assessed using pairwise multivariable Cox proportional hazards models. There were 2048 women and 308 men on BP and 1970 women and 1794 men who did not receive medication for osteoporosis. The relationship between BP and mortality risk was explored in three separate 1:1 propensity score-matched cohorts of BP users and no treatment (etidronate, n = 599, alendronate, n = 498, and risedronate n = 213). Nitrogen BP (n-BP) (alendronate and risedronate) was associated with lower mortality risks [pairwise HR, 0.66 (95% CI, 0.48-0.91)] while the less potent non-n-BP, etidronate, was not [pairwise HR: 0.89 (95% CI, 0.66-1.20)]. A direct comparison between n-BP and etidronate (n = 340 pairs) also suggested a better survival for n-BP [paired HR, 0.47 (95%CI, (95% CI, 031-0.70)] for n-BP vs. etidronate]. Compared to no treatment, nitrogen but not non-nitrogen bisphosphonates appear to be associated with better survival.

Research

DIR Jahrbuch 2018 (Deutsches IVF-Register Annual Report 2018)

Deutsches IVF-Register e.V., 2019Deutsches IVF-Register Jahrbuch

Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2018. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).

Research

CARTR Plus 2019 Annual Report (2018 Data) - Canadian Assisted Reproductive Technologies Register Plus

Canadian Fertility and Andrology Society; BORN Ontario, 2019CFAS / BORN Ontario

CARTR Plus annual report containing final treatment cycle and pregnancy outcome data for 2016 and preliminary treatment cycle data for 2017. Presented at the Canadian Fertility and Andrology Society Annual Meeting (Montreal, September 2018). The Canadian Assisted Reproductive Technologies Register Plus (CARTR Plus) is a voluntary professional society database operated by CFAS in collaboration with BORN Ontario, capturing IVF/ART cycle outcomes from Canadian fertility clinics.

Research

Fertility Treatment Options for Women With Polycystic Ovary Syndrome

Sawant S et al., 2019Clinical medicine insights. Reproductive health

Polycystic ovary syndrome is the most common endocrinological disorder in women of reproductive age. It is commonly associated with anovulatory subfertility, for which there are a range of treatment options available to help them conceive. These options are given in a step-wise manner with an appropriate selection of patients to maximise success rates with minimal complications. This review discusses the importance and involvement of multidisciplinary care when offering treatment to women with subfertility. Multidisciplinary care gives an excellent opportunity to identify, assess risk, and potentially prevent future morbidities and complications while treating women for fertility issues. We have also summarised the various options available pharmacological treatments, nonpharmacological intervention, and assisted reproductive technology.

Research

Can ovarian aging be delayed by pharmacological strategies?

Zhang J et al., 2019Aging

1. Aging (Albany NY). 2019 Jan 23;11(2):817-832. 10.18632/aging.101784. Can ovarian aging be delayed by pharmacological strategies? Zhang J(1), Chen Q(1), Du D(1), Wu T(1), Wen J(1), Wu M(1), Zhang Y(1), W(1), Zhou S(1), Li Y(1), Jin Y(1), Luo A(1), Wang S(1). (1)Department of Obstetrics and Gynecology, Tongji Hospital, College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Aging has been regarded as a treatable condition, prevent some diseases. Ovarian aging, a special type of organ senescence, earliest-aging organ, as ovaries exhibit an characteristics of gradual declines in ovarian since birth, compared to other organs. Ovarian pacemaker of female body aging, which drives the aging body. Hence, anti-ovarian aging has become a research to both biomedical scientists and pharmaceutical industry. A been made in exploration of possible anti-ovarian agents or approaches, calorie restriction mimetics, antioxidants, autophagy inducers etc., past years. This review is attempted to discuss anti-ovarian aging pharmacology and to offer understanding of molecular mechanisms underlying ovarian aging, informative for future prevention and treatment of diseases. 10.18632/aging.101784 PMC6366956 30674710 [Indexed for MEDLINE] CONFLICTS The conflicts of interest.

Research

Human health risks due to exposure to inorganic and organic chemicals from textiles: A review

Rovira J et al., 2019Environmental Research

It is well known that a number of substances used in the textile industry can mean not only environmental, but also health problems. The scientific literature regarding potential adverse health effects of chemical substances in that industry is mainly related with human exposure during textile production. However, information about exposure of consumers is much more limited. Although most research on the health effects of chemicals in textiles concern allergic skin reactions, contact allergy is not the only potential human health problem. In this paper, we have reviewed the current scientific information regarding human exposure to chemicals through skin-contact clothes. The review has been focused mainly on those chemicals whose probabilities of being detected in clothes were rather higher. Thus, we have revised the presence of flame retardants, trace elements, aromatic amines, quinoline, bisphenols, benzothiazoles/benzotriazoles, phthalates, formaldehyde, and also metal nanoparticles. Human dermal exposure to potentially toxic chemicals through skin-contact textiles/clothes shows a non-negligible presence in some textiles, which might lead to potential systemic risks. Under specific circumstances of exposure, the presence of some chemicals might mean non-assumable cancer risks for the consumers.

Research

Low Dose Naltrexone in Pregnancy

Boyle PC, 2019

Presentation examining the safety and potential benefits of low-dose naltrexone (LDN) use during pregnancy. Reports on a patient survey of 237 successful pregnancies comparing outcomes between LDN users and non-users. safety of LDN in pregnancy, additional benefits to mother and baby, and optimal duration of treatment. Findings suggest LDN is safe during pregnancy with trends toward improved outcomes (reduced prematurity, fewer SCBU admissions, fewer complications) for those continuing LDN beyond 26 weeks, though results did not achieve statistical significance. Also discusses potential epigenetic benefits of LDN for reducing endometriosis expression in the next generation and possible reduction of autism risk through immune modification.

InfertilityUltrasound SafetyBioeffects and SafetyUltrasound Exposure

Ultrasound in reproductive medicine: is it safe?

Abramowicz JS, 2019Ultrasound Imaging in Reproductive Medicine

Ultrasound is a form of energy with effects in tissues it traverses (bioeffects). The major bioeffects are a rise in temperature (thermal effects) and some effects secondary to the alternating positive and negative pressures of the ultrasound wave (nonthermal or mechanical effects). Two on-screen indices, the thermal index (TI) and the mechanical index (MI), give the end user an indication of possible thermal and nonthermal changes occurring in real time during the ultrasound scan. No harmful effects have been described in epidemiological studies in humans, but some deleterious results have been demonstrated in animals. While intensities produced by B-mode, gray-scale ultrasound are, most likely, safe, the use of Doppler involves much higher levels of energy. In addition, the very early fetus is known to be very vulnerable to external influences or insults. Information on susceptibility of the ovum, preor postfertilization, is virtually inexistent. In addition, knowledge regarding bioeffects and safety of ultrasound by clinical end users is grossly inadequate. In vivo exposure to ultrasound at spatial average intensities below 1 W/cm2, which is, arguably, almost always the case in ART as well as early gestation, does not adversely affect oocytes/embryos/fetuses. It is advocated to utilize ultrasound only when medically indicated, for the shortest time and at the lowest intensity compatible with accurate diagnosis. The TI and MI should be kept below 1. Further prospective studies on ultrasound safety in ART and pregnancy are highly recommended, as is education of the end users.

Research

Complementary and Alternative Medicine for Menopause

Johnson A et al., 2019Journal of evidence-based integrative medicine

Menopause is associated with problematic symptoms, including hot flashes, sleep problems, mood disorders, sexual dysfunction, weight gain, and declines in cognitive functioning. Many women seek complementary and alternative medicine (CAM) for symptom management. This article critically reviews the existing literature on CAM treatments most commonly used for menopausal symptoms. Electronic searches were conducted to identify relevant, English-language literature published through March 2017. Results indicate that mind and body practices may be of benefit in reducing stress and bothersomeness of some menopausal symptoms. In particular, hypnosis is a mind-body intervention that has consistently shown to have a clinically significant effect on reducing hot flashes. Evidence is mixed in regard to the efficacy of natural products and there are some safety concerns. Health care providers should consider the evidence on CAM in providing an integrative health approach to menopausal symptom management.

Research

Thoracic Endometriosis Syndrome: A Review of Diagnosis and Management

Nezhat C et al., 2019JSLS : Journal of the Society of Laparoendoscopic Surgeons

Endometriosis is characterized by the presence of endometrial-like glands and stroma outside the uterine cavity and is believed to affect 6%-10% of reproductive-age women. Endometriosis within the lung parenchyma or on the diaphragm and pleural surfaces produces a range of clinical and radiological manifestations. This includes catamenial pneumothorax, hemothorax, hemoptysis, and pulmonary nodules, resulting in an entity known as thoracic endometriosis syndrome (TES). Computerized searches of MEDLINE and PubMed were conducted using the key words "thoracic endometriosis," "catamenial pneumothorax," "catamenial hemothorax," and "catamenial hemoptysis." References from identified sources were manually searched to allow for a thorough review. TES can produce incapacitating symptoms for some patients. Symptoms of TES are nonspecific, so a high degree of clinical suspicion is warranted. Medical management represents the first-line treatment approach. When this fails or is contraindicated, definitive surgical treatment for cases of suspected TES uses a combined video laparoscopy performed by a gynecologic surgeon and video-assisted thoracoscopic surgery performed by a thoracic surgeon. Postoperative hormonal suppression may further reduce disease recurrence.

Research

Risk of stillbirth in low-risk singleton term pregnancies following fertility treatment: a national cohort study

Bay B et al., 2019BJOG : an international journal of obstetrics and gynaecology

To assess the risk of stillbirth in low-risk in vitro fertilisation (IVF) pregnancies. Register-based national cohort study. Denmark 2003-2013. Cohort of 425 732 singleton pregnancies including 10 235 conceived following IVF/intracytoplasmic sperm injection (ICSI), 4521 conceived following intrauterine insemination (IUI), and 410 976 spontaneously conceived. Information on pregnancy, obstetrical risk factors, stillbirth, and fertility treatment was obtained from the Danish national health registers for all pregnancies after gestational week 21+6 . We estimated the overall and gestational age-specific risk of stillbirth in low-risk term pregnancies following IVF, ICSI, and IUI. Further, we estimated the association between stillbirth and IVF and ICSI respectively as well as fresh or frozen-thawed embryo transfer. Risk of stillbirth. The number of stillbirths in spontaneously conceived and IVF/ICSI low-risk term pregnancies was 525 (0.1%) and 35 (0.3%), respectively. In multivariate analysis, the risk of stillbirth in pregnancies following IVF/ICSI was increased (odds ratio 2.1, 95% CI 1.4-3.1). The risk of stillbirth was correspondingly increased in time-to-event analyses taking risk time for each fetus into account from gestational week 37 and onwards (hazard ratio 2.4, 95% CI 1.6-3.6). In sub-analyses, the risk of stillbirth was increased for pregnancies following ICSI (odds ratio 2.2, 95% CI 1.2-3.1), but not IVF (odds ratio 1.7, 95% CI 0.9-3.1). We found a systematically increased risk of stillbirth in low-risk term pregnancies following IVF/ICSI. Whether the risk was related to the treatment or to underlying subfertility is uncertain. The results may indicate a need for obstetrical surveillance for these pregnancies when reaching term. Increased risk of stillbirth in low-risk term pregnancies following fresh cycle IVF/ICSI.

Research

Endometriosis as a Comorbid Condition in Chronic Fatigue Syndrome (CFS): Secondary Analysis of Data From a CFS Case-Control Study

Boneva RS et al., 2019Frontiers in pediatrics

Endometriosis (EM) is a recognized co-morbid condition in women with chronic fatigue syndrome (CFS). This analysis evaluates the impact of EM on the health of women with CFS by comparing selected health characteristics and laboratory parameters in women with CFS with and without EM (CFS+EM and CFS-only). This secondary analysis included all 36 women with CFS from a cross-sectional study of CFS in Wichita, KS, conducted between 2002 and 2003. The health characteristics and laboratory parameters of interest included functioning, fatigue, CFS-related symptoms, gynecologic history, routine laboratory parameters, inflammatory markers, cortisol levels, allostatic load, and sleep parameters (overnight polysomnography). We used parametric or non-parametric tests to compare group differences in the selected health characteristics and laboratory parameters. For examining the association between EM and variables of interest, logistic regression models were performed and odds ratios (OR) with 95% confidence intervals (CI) were reported for the magnitude of associations. Statistical significance was set at 0.05 (two-sided). The mean age of this study sample was 50.9 years. Of women with CFS, 36.1% reported having EM. Age and body mass index (BMI) did not differ between CFS+EM and CFS-only groups. When examining the impact of EM, compared to women with CFS-only, women with both CFS and EM were more likely to report chronic pelvic pain [OR = 9.00 (95% CI, 1.47-55.25)] and hysterectomy [OR = 10.3 (1.82-58.39)], had more CFS symptoms (6.8 ± 0.3 vs. 5.5 ± 0.3, p = 0.02), younger mean age at menopause onset (36.4 ± 3.0 vs. 47.0 ± 2.7 years, p = 0.03), higher mean number of obstructive apnea episodes per hour (20.3 vs. 4.4, p = 0.05) and reported more negative life events (15.8 vs. 4.4, p = 0.05). Other parameters did not differ significantly between the two groups. We found more than a third of women with CFS reported endometriosis as a comorbid condition. The endometriosis comorbidity was associated with chronic pelvic pain, earlier menopause, hysterectomy, and more CFS-related symptoms. However, endometriosis in women with CFS did not appear to further impact functioning, fatigue, inflammatory markers, or other laboratory parameters. Further investigations including younger women are warranted.

Research

Binge eating in patients with polycystic ovary syndrome: prevalence, causes, and management strategies

Krug I et al., 2019Neuropsychiatric disease and treatment

Emerging evidence suggests that disordered eating, particularly binge-eating symptomatology, is overrepresented within Polycystic Ovary Syndrome (PCOS) populations. This comorbidity presents a clinical dilemma as current treatment approaches for PCOS emphasize the importance of weight management, diet, exercise, and the potential for harm of such treatment approaches in PCOS patients with comorbid disordered eating. However, limited research has assessed the occurrence of binge eating and disordered eating in PCOS patients. Consequently, little is known about the prevalence of binge eating in PCOS, and the possible etiological processes to explain this comorbidity remain poorly understood. Given the paucity of research on this topic, the aims of this 1) to outline the main symptoms of PCOS and binge eating; 2) to provide an overview of the prevalence of binge eating in PCOS; 3) to outline possible etiological factors for the comorbidity between PCOS and binge eating; and 4) to provide an overview of management strategies of binge eating in PCOS.

Research

Postpartum depression and vitamin D: A systematic review

Amini S et al., 2019Critical reviews in food science and nutrition

Postpartum depression (PPD) is a prevalent mood disorder estimated to affect 20%-40% of women worldwide after childbirth. In recent studies, the effect of vitamin D on prevention of mood disorders and depression has been investigated, but it is still unclear how vitamin D may affect PPD. The evidence on the relevance between vitamin D deficiency and PPD is inconsistent, and assessment of the recent literature has not previously been carried out. Moreover, there are few clinical studies on PPD and vitamin D supplementation. Five studies have so far assessed the relationship between the levels of vitamin D and PPD. Findings from cohort studies suggest that vitamin-D deficiency is related to the incidence of PPD and vitamin D may play a significant role in the recovery of women with PPD, but it is uncertain whether these actions are the effect of vitamin D on the function of hypothalamic-pituitary-adrenal (HPA) axis, the levels of estradiol, serotonin, pro-inflammatory cytokines, and/or of other mechanisms involved in PPD.

Research

Recent advances in understanding and managing adenomyosis

Vannuccini S et al., 2019F1000Research

Adenomyosis is a benign uterine disorder in which endometrial glands and stroma are pathologically demonstrated in the uterine myometrium and it is considered a specific entity in the PALM-COEIN FIGO (polyp; adenomyosis; leiomyoma; malignancy and hyperplasia; coagulopathy; ovulatory dysfunction; endometrial; iatrogenic; and not yet classified - International Federation of Gynecology and Obstetrics) classification of causes of abnormal uterine bleeding (AUB). Although it has always been considered the classic condition of multiparous women over 40 years old who have pain and heavy menstrual bleeding, diagnosed at hysterectomy, the epidemiological scenario has completely changed. Adenomyosis is increasingly identified in young women with pain, AUB, infertility, or no symptoms by using imaging techniques such as transvaginal ultrasound and magnetic resonance. However, there is no agreement on the definition and classification of adenomyotic lesions from both the histopathology and the imaging point of view, and the diagnosis remains difficult and unclear. A uniform and shared reporting system needs to be implemented in order to improve our understanding on imaging features, their relationship with pathogenic theories, and their importance in terms of clinical symptoms and response to treatment. In fact, adenomyosis pathogenesis remains elusive and not a single theory can explain all of the different phenotypes of the disease. Furthermore, adenomyosis often coexists with other gynecological conditions, such as endometriosis and uterine fibroids, increasing the heterogeneity of available data. Treatment requires a lifelong management plan as the disease has a negative impact on quality of life in terms of menstrual symptoms, fertility, and pregnancy outcome and has a high risk of miscarriage and obstetric complications.

Research

The effect of vitamin D supplementation on the size of uterine leiomyoma in women with vitamin D deficiency

Hajhashemi M et al., 2019Caspian journal of internal medicine

Uterine leiomyomas (fibroids) are the most common benign pelvic tumors in women of reproductive age with an incidence ranging from 5.4% to 77%, Also, there is a high prevalence of vit D deficiency in Iran and there are the numbers of in vivo and vitro biological studies on the relationship of vitamin D and uterine leiomyomas. The aim of this study was to evaluate the effect of vit D supplementation on the size of uterine leiomyoma in women with vit D deficiency. This double-blind prospective clinical trial was performed on 69 patients with uterine leiomyomas who had vit D deficiency. Group A (n=35) was treated with vit D 50,000 IU every 2 weeks for 10 weeks, while group B (n=34) received placebo with same color and shape. Finally, the leiomyoma size in both groups was compared (IRCT: 20160521027998N5). After a 10-week intervention, 25-hydroxyvitamin D3 levels were significantly higher in group receiving vitamin D (36.08 vs 16.25 ng/ml). (P<0.001) Leiomyomas size in vit D group significantly decreased as compared to placebo group (52.58 vs 61.11 mm, respectively). Our results showed that administration of vit D3 may reduce the size of leiomyoma. It seems that vitamin D administration is the effective way to treat leiomyoma.

Research

Assisted Reproductive Technology Surveillance - United States, 2016

Sunderam S et al., 2019Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002)

Assisted Reproductive Technology Surveillance - United States, 2016. Sunderam S(1), Kissin DM(1), Zhang Y(1), Folger SG(1), Boulet SL(2), Warner L(1), Callaghan WM(1), Barfield WD(1). (1)Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, CDC. (2)Emory University School of Medicine, Atlanta, Georgia. Since the first U.S. infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Although the majority of infants conceived through ART are singletons, women who undergo ART procedures are more likely than women who conceive naturally to deliver multiple-birth infants. Multiple births pose substantial risks for both mothers and infants, including obstetric complications, preterm delivery (<37 weeks), and low birthweight (<2,500 g). This report provides state-specific information for the United States (including the District of Columbia and Puerto Rico) on ART procedures performed in 2016 and compares birth outcomes that occurred in 2016 (resulting from ART procedures performed in 2015 and 2016) with outcomes for all infants born in the United States in 2016. 2016. In 1995, CDC began collecting data on ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (FCSRCA) (Public Law 102-493 [October 24, 1992]). Data are collected through the National ART Surveillance System (NASS), a web-based data collection system developed by CDC. This report includes data from 52 reporting areas (the 50 states, the District of Columbia, and Puerto Rico). In 2016, a total of 197,706 ART procedures (range: 162 in Wyoming to 24,030 in California) with the intent to transfer at least one embryo were performed in 463 U.S. fertility clinics and reported to CDC. These procedures resulted in 65,964 live-birth deliveries (range: 57 in Puerto Rico to 8,638 in California) and 76,892 infants born (range: 74 in Alaska to 9,885 in California). Nationally, the number of ART procedures performed per 1 million women of reproductive age (15-44 years), a proxy measure of the ART use rate, was 3,075. ART use rates exceeded the national rate in 14 reporting areas (Connecticut, Delaware, the District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Utah, and Virginia). ART use exceeded 1.5 times the national rate in nine states, including three (Illinois, Massachusetts, and New Jersey) that also had comprehensive mandated health insurance coverage for ART procedures (i.e., coverage for at least four oocyte retrievals). Nationally, among ART transfer procedures for patients using fresh embryos from their own eggs, the average number of embryos transferred increased with increasing age (1.5 among women aged <35 years, 1.7 among women aged 35-37 years, and 2.2 among women aged >37 years). Among women aged <35 years, the national elective single-embryo transfer (eSET) rate was 42.7% (range: 8.3% in North Dakota to 83.9% in Delaware). In 2016, ART contributed to 1.8% of all infants born in the United States (range: 0.3% in Puerto Rico to 4.7% in Massachusetts). ART also contributed to 16.4% of all multiple-birth infants, including 16.2% of all twin infants and 19.4% of all triplets and higher-order infants. ART-conceived twins accounted for approximately 96.5% (21,455 of 22,233) of all ART-conceived infants born in multiple deliveries. The percentage of multiple-birth infants was higher among infants conceived with ART (31.5%) than among all infants born in the total birth population (3.4%). Approximately 30.4% of ART-conceived infants were twins and 1.1% were triplets and higher-order infants. Nationally, infants conceived with ART contributed to 5.0% of all low birthweight (<2,500 g) infants. Among ART-conceived infants, 23.6% had low birthweight compared with 8.2% among all infants. ART-conceived infants contributed to 5.3% of all preterm (gestational age <37 weeks) infants. The percentage of preterm births was higher among infants conceived with ART (29.9%) than among all infants born in the total birth population (9.9%). The percentage of ART-conceived infants who had low birthweight was 8.7% among singletons, 54.9% among twins, and 94.9% among triplets and higher-order multiples; the corresponding percentages among all infants born were 6.2% among singletons, 55.4% among twins, and 94.6% among triplets and higher-order multiples. The percentage of ART-conceived infants who were born preterm was 13.7% among singletons, 64.2% among twins, and 97.0% among triplets and higher-order infants; t

InfertilityPlatelet-Rich Plasma TreatmentExperimental RejuvenationFertility Restoration Open Access

Autologous Platelet-Rich Plasma Treatment Enables Pregnancy for a Woman in Premature Menopause

Sfakianoudis K et al., 2018J Clin Med

This report presents the case of a woman aged 40 who has experienced premature menopause from the age of 35. Having rejected oocyte donation, she opted for intraovarian injection of autologous platelet-rich plasma with the aim to rejuvenate the ovarian tissue and enable the employment of her own gametes through in-vitro fertilization. Six weeks following the autologous platelet-rich plasma treatment, a significant reduction in the patient's follicle-stimulating hormone (FSH) levels were noted. A natural in-vitro fertilization cycle led to a biochemical pregnancy, resulting in a spontaneous abortion at the 5th week of pregnancy. This is the first report of a successful autologous platelet-rich plasma application leading to pregnancy in menopause. This report uniquely contributes to the medical knowledge and challenges current practice in the context of infertility. The efficiency and safety of this treatment with regard to the reproductive system merits further investigation.

PregnancyPrevention and TreatmentInositolRandomized Controlled Trial

The influence of different inositol stereoisomers supplementation in pregnancy on maternal gestational diabetes mellitus and fetal outcomes in high-risk patients: a randomized controlled trial

Celentano C et al., 2018J Matern Fetal Neonatal Med

To identify the effects of different dietary inositol stereoisomers on insulin resistance and the development of gestational diabetes mellitus (GDM) in women at high risk for this disorder.Design: A preliminary, prospective, randomized, placebo controlled clinical trial. Nonobese singleton pregnant women with an elevated fasting glucose in the first or early second trimester were studied throughout pregnancy. Supplementation with myo-inositol, d-chiro-inositol, combined myoand d-chiro-inositol or placebo.Main Development of GDM on a 75 grams oral glucose tolerance test at 24-28 weeks' gestation. Secondary outcome measures were increase in BMI, need for maternal insulin therapy, macrosomia, polyhydramnios, neonatal birthweight and hypoglycemia. The group of women allocated to receive myo-inositol alone had a lower incidence of abnormal oral glucose tolerance test (OGTT). Nine women in the control group (C), one of the myo-inositol (MI), five in d-chiro-inositol (DCI), three in the myo-inositol/D-chiro-inositol group (MI/DCI) required insulin (p = .134). Basal, 1-hour, and 2 hours glycemic controls were significantly lower in exposed groups (p < .001, .011, and .037, respectively). The relative risk reduction related to primary outcome was 0.083, 0.559, and 0.621 for MI, DCI, and MI/DCI groups. This study compared the different inositol stereoisomers in pregnancy to prevent GDM. Noninferiority analysis demonstrated the largest benefit in the myo-inositol group. The relevance of our findings is mainly related to the possibility of an effective approach in GDM. Our study confirmed the efficacy of inositol supplementation in pregnant women at risk for GDM.

Fertility AwarenessSmartphone Ovulation DetectionSalivary Ferning Point-of-CareAffordable Fertility Monitoring

An inexpensive smartphone-based device for point-of-care ovulation testing

Potluri V et al., 2018Lab Chip

The ability to accurately predict ovulation at-home using low-cost point-of-care diagnostics can be of significant help for couples who prefer natural family planning. Detecting ovulation-specific hormones in urine samples and monitoring basal body temperature are the current commonly home-based methods used for ovulation detection; however, these methods, relatively, are expensive for prolonged use and the results are difficult to comprehend. Here, we report a smartphone-based point-of-care device for automated ovulation testing using artificial intelligence (AI) by detecting fern patterns in a small volume (<100 μL) of saliva that is air-dried on a microfluidic device. We evaluated the performance of the device using artificial saliva and human saliva samples and observed that the device showed >99% accuracy in effectively predicting ovulation.

Research

Fertility and infertility: Definition and epidemiology

Vander Borght M et al., 2018Clinical Biochemistry

Infertility is a disease characterized by the failure to establish a clinical pregnancy after 12 months of regular and unprotected sexual intercourse. It is estimated to affect between 8 and 12% of reproductive-aged couples worldwide. Males are found to be solely responsible for 20-30% of infertility cases but contribute to 50% of cases overall. Secondary infertility is the most common form of female infertility around the globe, often due to reproductive tract infections. The three major factors influencing the spontaneous probability of conception are the time of unwanted non-conception, the age of the female partner and the disease-related infertility. The chance of becoming spontaneously pregnant declines with the duration before conception. The fertility decline in female already starts around 25-30 years of age and the median age at last birth is 40-41 years in most studied populations experiencing natural fertility. The disease-related infertility may affect both genders or be specific to one gender. The factors affecting both genders' fertility are hypogonadotrophic hypogonadism, hyperprolactinemia, disorders of ciliary function, cystic fibrosis, infections, systemic diseases and lifestyle related factors/diseases. Premature ovarian insufficiency, polycystic ovary syndrome, endometriosis, uterine fibroids and endometrial polyps may play a role in female infertility. Male infertility may be due to testicular and post-testicular deficiencies. Semen decline that has been observed over the years, endocrine disrupting chemicals and consanguinity are other factors that may be involved.

Research

Observational retrospective study of US national utilisation patterns and live birth rates for various ovarian stimulation protocols for in vitro fertilisation

Kushnir VA et al., 2018BMJ Open

Alternative ovarian stimulation protocols for in vitro fertilisation (IVF) have grown in popularity. Yet, patient populations best suited for these protocols have not been defined. Our objective was, therefore, to determine national IVF utilisation patterns and live birth rates of various ovarian stimulation protocols. Retrospective cohort study. Academic-affiliated private fertility centre. Aggregate data published by Society for Assisted Reproductive Technology for autologous IVF cycles performed in the USA during 2014 and 2015 were analysed. IVF cycles were stratified based on 205 705 conventional stimulations, 4397 minimal stimulations, 2785 natural cycles and 514 in vitro maturation (IVM) cycles. Repeat cycles could not be determined in this analysis. Utilisation patterns and age-specific live birth rates for various ovarian stimulation protocols. With advancing female age, utilisation of conventional stimulation protocols decreased, while minimal stimulation and natural cycle IVF increased. Diminished ovarian reserve diagnoses were in all age groups less prevalent in patients undergoing conventional stimulation than with all other protocols. Live birth rates were highest with conventional stimulation at 42.4%, 33.1%, 22.1%, 11.7% and 3.9% for <35, 35-37, 38-40, 41-42 and >42 female age groups, respectively. The difference in live birth rates between conventional stimulation and other protocols widened with advancing age from 1.6-fold to 3.9-fold among women <35 years of age, reaching 4.4-fold to 6.6-fold among women >42 years of age. In comparison to conventional stimulation IVF-minimal stimulation, natural cycle IVF and IVM protocols offer lower but still acceptable live birth rates among young women. These alternative protocols are frequently used in older women and those with diminished ovarian reserve, despite their lower live birth rates. The reasons for this apparent incongruity warrant further careful exploration.

Ethics/PhilosophyHumanae Vitae ConsequencesDemographic and Family EffectsMarriage and Complementarity

Rejecting Humanae Vitae: The Social Costs of Denying the Obvious

Klaus H, 2018Linacre Q

Since contraceptives have been used to remove fertility from the conjugal act, the social consequences predicted in the encyclical Humanae vitae, such as the rise in cohabitation, decline of marriage, rise of divorce, and single parenthood, have exceeded expectations. The degradation of the sexual act from total mutual self-giving to momentary union has led to doubting the significance of the biological truth of the body and opened the door to gender fluidity. Promiscuity became normative, and the need for consent became eroded until women revolted with the #MeToo movement. Promiscuity, cohabitation, and divorce have resulted in 40 percent of children born to unmarried parents whose tenuous unions often leave the children in melded and dysfunctional families. Relation-free "hookups" have become the norm among young adults, leaving a flood of emotionally damaged women, an epidemic of sexually transmitted infections, and unplanned pregnancies, to which the healthcare industry has responded by doubling down on the means which caused the problem in the first place with near-coercive promotion of long-acting, reversible contraceptives (LARCs). LARCs must be inserted and removed professionally and make reproductive choice moot. Respecting the truth of the body is the precise counter measure. A woman's cyclic fertility is easily observed with reliable biomarkers-natural family planning-which requires the whole person. Fertility awareness-based methods of family planning have no side effects, are easy to learn, and can be used to achieve as well as delay conception. The self-discovery inherent in learning fertility literacy has empowered adolescent girls and boys to understand and value their sexuality and fertility and avoid choosing harmful behaviors. Why does society continue to treat fertility as if it were a disease? Removing the idea of pregnancy from the sexual act as the result of readily available contraception has effectively limited choices about sexual behavior to the satisfaction of momentary desires. As Humanae vitae predicted, fewer marriages were contracted, divorce increased and now 40% of children are born out of wedlock despite extensive public education campaigns to promote contraception. Side effects of the hormonal pill have reduced their use so health care professionals have doubled down, providing long acting contraceptives which do not require the user to exercise choice before each act of intercourse, or of taking a pill. There is a much better way to regulate births-to learn to read the book of nature. Fertility is not a disease to be removed from the body. All that is needed is to understand the natural signs of fertility-natural family planning, now called FABM-Fertility Awareness-Based Methods. These have no side effects, enhance couple communication and offer effective choice for child spacing and demonstrably support premarital chastity for teens.

Fertility AwarenessCervical Mucus-Hormone DissociationBreastfeeding Hormonal PatternsUrinary Hormone Validation

Dissociation between Cervical Mucus and Urinary Hormones during the Postpartum Return of Fertility in Breastfeeding Women

Bouchard T et al., 2018Linacre Q

Identifying the return of fertility with cervical mucus observations is challenging during the postpartum period. Use of urinary measurements of estrogen and progesterone can assist in understanding the return to fertility during this period. The purposes of this study were to describe the postpartum return of fertility by an analysis of total estrogen (TE) and pregnanediol glucuronide (PDG) profiles and to correlate these profiles with cervical mucus observations. Twenty-six participants collected urine samples during the postpartum period and recorded mucus scores. TE and PDG hormones were analyzed and compared with mucus scores. During amenorrhea, mucus reflected TE changes in only 35 percent of women; after amenorrhea, typical mucus patterns were seen in 33 percent of cycles. We concluded that postpartum mucus and hormone profiles are significantly dissociated but that monitoring urinary hormones may assist in identifying the return of fertility. We also identified different hormonal patterns in the return to fertility. The postpartum period is a challenging time for identifying the return of fertility. The purposes of this study were to describe the hormonal patterns during the return of fertility and to correlate these patterns with cervical mucus observations. Twenty-six postpartum women collected urine samples and recorded mucus scores. Urinary estrogen and progesterone hormones were analyzed and compared with mucus scores. Before the return of menses, mucus reflected hormonal changes in only 35 percent women and after first menses in 33 percent of cycles. We found that hormone profiles do not correlate well with mucus observations during the postpartum return of fertility.

Contraception/ComparisonVenous ThromboembolismContraception SafetyHormonal Contraception

Systematic Review of Hormonal Contraception and Risk of Venous Thrombosis

Keenan L et al., 2018Linacre Q

Hormonal contraception (HC) is widely used throughout the world and has been associated with venous thrombosis (VT) such as deep vein thrombosis, pulmonary emboli, and cerebral VT. To provide a current comprehensive overview of the risk of objectively confirmed VT with HC in healthy women compared to nonusers. PubMed was searched from inception to April 2018 for eligible studies in the English language, with hand searching from past systematic reviews. We selected original research evaluating risk of objectively confirmed VT in healthy women taking oral or nonoral HC compared with nonusers. The primary outcome of interest was a fatal or nonfatal VT in users of HC compared to nonusers or past users. Studies with at least twenty events were eligible. Adjusted relative risks with 95 percent confidence intervals were reported. Three independent reviewers extracted data from selected studies. 1,962 publications were retrieved through the search strategy, with 15 publications included. Users of oral contraception with levonorgesterol had increased risk of VT by a range of 2.79-4.07, while other oral hormonal preparations increased risk by 4.0-48.6. Levonorgestrel intrauterine devices did not increase risk. Etonogestrel/ethinyl estradiol vaginal rings increased the risk of VT by 6.5. Norelgestromin/ethinyl estradiol patches increased risk of VT by 7.9. Etonogestrel subcutaneous implants by 1.4 and depot-medroxyprogesterone by 3.6. The risk of fatal VT was increased in women aged fifteen to twenty-four by 18.8-fold. Users of HC have a significant increased risk of VT compared to nonusers. Current risks would project at least 300-400 healthy young women dying yearly in the United States due to HC. Women should be informed of these risks and offered education in fertility-awareness-based methods with comparable efficacy for family planning. HC is widely used throughout the world and has been associated with blood clots in the legs and lungs. We searched the literature and found the risks of currently used forms of birth control increased between threeand ninefold for blood clots for healthy women. The risks found would project 300-400 women dying from using HC each year in the United States.

Contraception/ComparisonBreakthrough OvulationPost-Fertilization EffectsContraceptive Suppression

Systematic Review of Ovarian Activity and Potential for Embryo Formation and Loss during the Use of Hormonal Contraception

Harrison D et al., 2018Linacre Q

The purpose of this review was to determine whether there is evidence that ovulation can occur in women using hormonal contraceptives and whether these drugs might inhibit implantation. We performed a systematic review of the published English-language literature from 1990 to the present which included studies on the hormonal milieu following egg release in women using any hormonal contraceptive method. High circulating estrogens and progestins in the follicular phase appear to induce dysfunctional ovulation, where follicular rupture occurs but is followed by low or absent corpus luteum production of progesterone. Hoogland scoring of ovulatory activity may inadvertently obscure the reality of ovum release by limiting the term "ovulation" to those instances where follicular rupture is followed by production of a threshold level of luteal progesterone, sufficient to sustain fertilization, implantation, and the end point of a positive β-human chorionic gonadotropin. However, follicular ruptures and egg release with subsequent low progesterone output have been documented in women using hormonal contraception. In the absence of specific ovulation and fertilization markers, follicular rupture should be considered the best marker for egg release and potential fertilization. Women using hormonal contraceptives may produce more eggs than previously described by established criteria; moreover, suboptimal luteal progesterone production may be more likely than previously acknowledged, which may contribute to embryo loss. This information should be included in informed consent for women who are considering the use of hormonal contraception. For this study, the authors looked at English-language research articles that focused on how hormonal birth control, such as the birth control pill, may affect very early human embryos. The authors found that abnormal ovulation, or release of an egg followed by abnormal hormone levels, may often occur in women using hormonal birth control. This may increase the number of very early human embryos who are lost before a pregnancy test becomes positive. For women who are thinking about using hormonal birth control, this is important information to consider.

Ethics/PhilosophyHormonal Contraception Risk DisclosureComprehensive Risk OverviewPrescribing Transparency

Hormonal Contraception and the Informed Consent

Hilger DJ et al., 2018Linacre Q

Since the 1960s, hormonal contraceptives have become the most commonly used method of pregnancy prevention in the United States and the world. Oral contraceptives are used by a large percentage of women, including Christian women. There are known health risks to women demonstrated in research published since Pope Paul VI's prophetic encyclical Humanae vitae in 1968. These risks include venous thrombosis, cardiovascular risks, and an increased risk of cancer. These risks are medically recognized with continued scientific debate on the degree. The risks are significantly increased with preexisting conditions and in certain demographic groups. Discussing known and potential treatment risks is a standard that is both accepted by the medical community and is increasingly expected by patients. This discussion can be accomplished by the mechanism and principle of informed consent. Depending on the circumstances, abstinence or fertility awareness-based methods (FABMs) should be presented to patients. FABMs are licit, safe, and effective methods of pregnancy prevention. Informed consent is the most effective means of providing patients with pertinent information on the significant risks of contraception. This article discusses the use of the informed consent to provide patients with information on the medical and ethical risks of oral contraceptives. FABMs and abstinence are presented as effective, safe, and licit preferences to oral contraceptives. Discussing known and potential treatment risks is accepted by the medical community and expected by patients (shared decision making). The authors discuss the historical context of Pope Paul VI's encyclical Humanae vitae in relationship to the development and rapid adoption of oral contraceptives.

Fertility AwarenessNFP Science State AssessmentModern NFP EffectivenessFuture Research Priorities

The State of the Science of Natural Family Planning Fifty Years after Humane Vitae: A Report from NFP Scientists' Meeting Held at the US Conference of Catholic Bishops, April 4, 2018

Manhart MD et al., 2018Linacre Q

A one-day meeting of physicians, professional nurses, and scientists actively involved in Natural Family Planning (NFP) research was held to review the state of the science of NFP and consider future priorities. The (i) determine the gaps in research evidence for secure methods of NFP among women of all reproductive categories, (ii) determine the gaps in the research and development of new technology for providing NFP services, (iii) determine the gaps in the research that determine the benefits and challenges with use of NFP among married couples, and (iv) provide prioritized ideas for future research needs from the analysis of evidence gaps from objectives above. This article summarizes the discussion and conclusions drawn from topics reviewed. While much has been accomplished in the fifty years since Humane vitae, there are still many gaps to address. Five areas for future research in NFP were (1) well-designed method effectiveness studies among various reproductive categories including important subpopulations (postpartum, perimenopause, posthormonal contraceptive), normally cycling women (especially US women), and comparative studies between NFP methods; (2) validation studies to establish the benefit of charting fertility signs (both currently known and potential new indicators) as a screening tool for women's health issues; (3) ongoing independent evaluation of fertility monitoring apps to provide users perspective on the relative merits of each and to identify those most worthy of further effectiveness testing; (4) studies evaluating the impact of new technologies on NFP adoption, use, and persistence; and (5) creation of a shared database across various NFP methods to collaborate on shared research interests, longitudinal studies, and so on. This summarizes a meeting to review the scientific and medical progress related to natural family planning made in the 50 years since Humane Vitae and to define priorities for future work. Areas reviewed included the evidence for avoiding pregnancy in normally cycling, postpartum, and perimenopausal women, the impact of new technology, including fertility charting apps, on NFP, and the impact on relationships and personal well-being from use of NFP. Five priority focus areas for future research were also identified.

Ethics/PhilosophyReproductive Medicine Moral FrameworkHumanae Vitae Broad VisionAssisted Reproduction Moral Analysis

Bioethical and Moral Perspectives in Human Reproductive Medicine

Turner JV et al., 2018Linacre Q

A reductive reading of Humanae vitae seeks to limit its appeal to a ban on contraception. In truth, however, it offers a vision of human sexuality and conjugal love with broad and enduring relevance. In setting forth the intrinsic complementarity and irreducibility of the unitive and procreative dimensions of the conjugal act, Paul VI has given us a hermeneutical key for assessing many contemporary ethical dilemmas in human reproductive medicine. From this perspective, this article seeks to apply the logic of Humanae vitae to several real-life scenarios confronted by medical practitioners, educators, and ethicists working in the field of fertility and reproductive health. These include a consideration of the ethics of prescribing hormonal contraceptives, the possibilities of investigating male infertility, issues of cooperation in counseling and assisting conception in same-sex relationships, the ethics pertaining to assisted reproductive technology (ART), the contested case of prenatal adoption, and the application of double-effect reasoning. On the occasion of the fiftieth anniversary of the promulgation of Pope Paul VI's encyclical Humanae vitae, this article seeks to defend its enduring relevance to modern-day society, through application of its reasoning to contemporary dilemmas in reproductive medicine. It considers real cases of the ethics of prescribing hormonal contraceptives, of investigating male infertility, of cooperating in counseling and assisting conception in same-sex relationships, of ART, of prenatal adoption, and the application of double-effect reasoning.

PCOSMetabolic and Cardiovascular RiskPostmenopausal HealthPsychological Health

Beyond fertility: polycystic ovary syndrome and long-term health

Cooney LG et al., 2018Fertil Steril

Polycystic ovary syndrome (PCOS) is a reproductive, endocrine, and metabolic disorder affecting millions of women worldwide. Women with PCOS are often identified in adolescence or early adulthood with symptoms of oligomenorrhea or hirsutism or when presenting for infertility care. The health risks associated out of PCOS, however, go far beyond management of these common presenting symptoms or fertility treatment and likely extend past the reproductive years through and beyond menopause. International surveys suggest that most patients are dissatisfied with long-term counseling related to medical and psychologic issues. We performed a review of comorbidities, including diabetes mellitus, dyslipidemia, obesity, hypertension, metabolic syndrome, depression, anxiety, obstructive sleep apnea, nonalcoholic fatty liver disease, endometrial cancer, and cardiovascular disease, in both reproductive-age and older women with PCOS. Most meta-analyses in reproductive-age women demonstrate increased risks independent from obesity. Longitudinal and cross-sectional studies including women with PCOS >40 years of age are limited in number and design, but many demonstrate that some of these comorbidities persist. All providers involved in the multidimensional care of women with PCOS should be aware of these long-term health risks to provide appropriate counseling, screening, and management options. We identify limitations that should be the focus of future studies designed to study health outcomes in postmenopausal women with PCOS.